Experimental evidence indicates that factors other than, or in addition to, the functional state of the immune system are associated with the age-related increase in the frequency of incidence of neoplastic transformation observed in mammalian organisms. We propose that some as yet unknown fraction of this carcinoma results from age-related alterations in the metabolism of compounds which are chemical carcinogens. In order to test this hypothesis, we propose the following: 1) to determine aryl hydrocarbon hydroxylase activity (AHH), expoxide hydrase activity (EH), glutathione-S-arene-oxidase transferase activity, NADPH-cytochrome c reductase activity and P450 levels (where possible) in rodent lung, liver and skin, human skin, and human cultured leucocytes derived from organisms of different ages; 2) to determine the kinetics and magnitude of response of the above-mentioned enzymic functions in rodent lung and liver of animals of different ages following treatment with polycyclic hydrocarbons; 3) to determine the degree of functional linkage between EH and AHH in liver microsomes derived from rodents of different ages; 4) to determine cytochrome P488 content in liver microsomes derived from rodents of different ages; and 5) to determine the ability of liver microsomes derived from rodents of different ages to activate polycyclic hydrocarbons to chemical mutagens in a bacterial test system.